Abstract Study question Does maternal depression during early pregnancy affect fetal growth? Summary answer Maternal depression during early pregnancy is associated with increased fetal biometrics, higher birth weight, and also an elevated risk of macrosomia. What is known already Prenatal depression, a prevalent psychological condition occurring during pregnancy, affects approximately 7% to 25% of pregnant women. According to the developmental origins of health and disease theory, intrauterine adverse exposure, such as malnutrition and prenatal depression, may exert long-term effects by altering placental function and epigenetic modification. Growing evidence from epidemiologic studies has shown that maternal depression during mid-to-late stages of pregnancy may be associated with reduced fetal growth. However, the effect of depression may vary depending on the timing of intrauterine exposure. For early pregnancy depression, there is a limited number of studies examining its association with fetal growth. Study design, size, duration Prospective evaluation of the associations of maternal depression during early pregnancy with fetal growth and neonatal outcomes in 23,465 mothers. The study was conducted at a hospital-based center in Shanghai, China. The mothers were enrolled between March 2019 to April 2022. Participants/materials, setting, methods The Patient Health Questionnaire (PHQ-9) was used to screen for prenatal depression before 14 weeks’ gestational weeks. Fetal ultrasound parameters, including abdominal circumference(AC), head circumference(HC), femur length(FL),and humerus length(HL), along with birth outcomes were obtained from medical records. Estimated fetal weight(EFW) was calculated using the Hadlock formula. Differences in fetal growth trajectory of different maternal depressive statuses during three periods (16-23, 24-31, and 32-41 gestational weeks) were compared using a multilevel model with fractional polynomials. Main results and the role of chance In this prospective cohort study, maternal depressive symptoms affected 20402(13%) pregnant women during early pregnancy. Overall, compared to women without depressive symptoms, those with depressive symptoms during early pregnancy had higher longitudinal fetal trajectories, with an estimated increase in EFW (β = 0.33; 95% CI, 0.06-0.61), AC (β = 0.16; 95% CI, 0.04-0.29), HL (β = 0.14; 95% CI, 0.05-0.23), FL (β = 0.14; 95% CI, 0.03-0.25) and HL(β = 0.16; 95% CI, 0.04-0.27). Stratified by different gestational periods, the increments in HC (β = 0.16; 95% CI, 0.06-0.26), HL (β = 0.24; 95% CI, 0.11-0.38) and EFW (β = 0.60; 95% CI, 025-0.96) of women with depressive symptoms commenced after 32 weeks of gestational age and FL started after 24 gestational weeks (β = 0.24; 95% CI, 0.06-0.42 [24-31 weeks] and β = 0.19; 95% CI, 0.07-0.31 [32-41 weeks]). Notably, increases in AC among women with depressive symptoms were observed during 16-23 gestational weeks (β = 0.21; 95% CI, 0.04-0.39). What’s more, offspring born to mothers with early pregnancy depression had a significantly higher birth weight of 14.13g (95% CI, 1.33-27.81 g) and an increased risk of macrosomia (odds ratio, 1.21; 95% CI, 1.02-1.43). Limitations, reasons for caution A self-reported scale was used to assess the mental status of pariticipants, potentially introducing measurement bias. What’s more, long-term effects of early pregnancy depression on offspring were not explored due to the limited duration of follow-up thus far. Wider implications of the findings It may be necessary to reconsider the timing of prenatal depression screening and implement preventive measures during early pregnancy to mitigate excessive fetal growth. Further studies are warranted to validate the findings and supplement more biological evidence. Trial registration number not applicable